Group IIA secreted phospholipase A2 (PLA2G2A) hydrolyzes glycerophospholipids at the sn-2 position resulting in the release of fatty acids and lysophospholipids. C57BL/6 mice do not express Pla2g2a due to a frameshift mutation (wild-type [WT] mice). We previously reported that transgenic expression of human PLA2G2A in C57BL/6 mice (IIA+ mice) protects against weight gain and insulin resistance, in part by increasing total energy expenditure. Additionally, we found that brown and white adipocytes from IIA+ mice have increased expression of mitochondrial uncoupling markers, such as uncoupling protein 1 (UCP1), peroxisome proliferator-activated receptor-gamma coactivator, and PR domain containing 16, suggesting that the energy expenditure phenotype might be due to an increased thermogenic capacity in adipose tissue. Here, we further characterize the impact of PLA2G2A on thermogenic mechanisms in adipose tissue. Metabolic analysis of WT and IIA+ mice revealed that even when housed within their thermoneutral zone, IIA+ mice have elevated energy expenditure compared to WT littermates. Increased energy expenditure in IIA+ mice is associated with increased citrate synthase activity in brown adipose tissue (BAT) and increased mitochondrial respiration in both brown and white adipocytes. We also observed that direct addition of recombinant PLA2G2A enzyme to in vitro cultured adipocytes results in the marked induction of UCP1 protein expression. Finally, we report that PLA2G2A induces the expression of numerous transcripts related to energy substrate transport and metabolism in BAT, suggestive of an increase in substrate flux to fuel BAT activity. These data demonstrate that PLA2G2A enhances adipose tissue thermogenesis, in part, through elevated substrate delivery and increased mitochondrial content in BAT.

中文翻译：

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IIA 组分泌的磷脂酶 A2 (PLA2G2A) 增强脂肪组织产热

IIA 组分泌的磷脂酶 A2 (PLA2G2A) 在sn-2处水解甘油磷脂位置导致脂肪酸和溶血磷脂的释放。由于移码突变（野生型 [WT] 小鼠），C57BL/6 小鼠不表达 Pla2g2a。我们之前曾报道过，C57BL/6 小鼠（IIA+ 小鼠）中人 PLA2G2A 的转基因表达可防止体重增加和胰岛素抵抗，部分原因是通过增加总能量消耗。此外，我们发现来自 IIA+ 小鼠的棕色和白色脂肪细胞线粒体解偶联标记物的表达增加，例如解偶联蛋白 1 (UCP1)、过氧化物酶体增殖物激活受体-γ 共激活因子和含有 16 的 PR 域，表明能量消耗表型可能是由于脂肪组织的产热能力增加。在这里，我们进一步表征了 PLA2G2A 对脂肪组织中产热机制的影响。WT 和 IIA+ 小鼠的代谢分析表明，即使在它们的热中性区内，IIA+ 小鼠与 WT 同窝仔鼠相比能量消耗也有所增加。IIA+ 小鼠能量消耗的增加与棕色脂肪组织 (BAT) 中柠檬酸合酶活性的增加以及棕色和白色脂肪细胞中线粒体呼吸的增加有关。我们还观察到，将重组 PLA2G2A 酶直接添加到体外培养的脂肪细胞中会显着诱导 UCP1 蛋白表达。最后，我们报告说 PLA2G2A 在 BAT 中诱导与能量底物转运和代谢相关的许多转录本的表达，这表明底物通量增加以促进 BAT 活动。这些数据表明 PLA2G2A 部分地增强了脂肪组织的产热，